De novo mutations in SPG3A: a challenge in differential diagnosis and genetic counselling

Excerpt

Hereditary spastic paraplegias (HSPs) are genetically determined neurodegenerative disorders presenting with spasticity and progressive weakness predominantly affecting the lower limbs due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. Traditionally, HSPs can be divided into pure (uncomplicated) and complicated forms, depending on the presence of additional neurological and non-neurological features [1]. To date, about 70 HSPs gene loci have been mapped and all patterns of inheritance have been described [2]. Mutations in SPG3A/ATL1, encoding atlastin-1, cause both pure and complicated forms and represent the most common autosomal dominant (AD) HSP with onset before age 10 years [2]. The rate of progression is usually slow; wheelchair dependency or need for a support to walk is relatively rare [3]. Herein, we describe three patients with infantile onset HSP harbouring de novo mutations, including a new variant, in SPG3A/ATL1. …